A Spotlight on the Underlying Activation Mechanisms of the NLRP3 Inflammasome and its Role in Atherosclerosis: A Review

Abstract

The world's number one cause of death is cardiovascular diseases. The pathogenesis of different disease entities in the cardiovascular disease spectrum is complicated and multifactorial. Inflammation in these complicated etiologies serves as a key position and is a significant cause of atherosclerosis, which contributes to the underlying pathology. Therefore, therapeutic targeting of inflammatory pathways in patients with cardiovascular diseases such as atherosclerosis enhances cardiovascular results. Inflammasomes are intracellular protein complexes engaged in atherosclerosis pathogenesis and activated by multiple danger signals. Emerging proof has revealed that Nod-like receptor protein 3 (NLRP3) inflammasome, which regulates caspase-1 activation and later pro-interleukin processing, triggers inflammatory reactions in the vascular wall and leads to atherosclerotic plaque formation. Inflammasome-mediated signaling interference could decrease inflammation and mitigate illness severity. In this section, we provide an overview of the present literature on the underlying mechanisms leading to the activation of NLRP3 inflammasome and the role of NLRP3 inflammasome in the progression of atherogenesis and highlight the possibility of therapeutic interventions due to mechanisms involved in the of inhibition of NLRP3 activation.

Inflammation and atherosclerosis: signaling pathways and therapeutic intervention

“… 150 The NLRP3 inflammasome (LRR, NACHT, and PYD domains-containing protein 3) that is well known, senses the endogenous danger signal activated by cholesterol crystals, activates caspase-1 to cleave pro-IL-1β and pro-IL-18 into mature and biologically active IL-1β and IL-18. 122 , 151 The NLRP3 inflammasome is highly expressed in a variety of cell types, including innate immune cells and non-immune cells involved in the pathogenesis of the atherosclerotic cardiovascular disease. 152 – 154…”

NLRP3-Mediated Inflammation in Atherosclerosis and Associated Therapeutics

“…Components of NLRP3 complex have been reported to be constitutively expressed in both innate and adative immune cells like monocytes, macrophages, dendritic cells and T cells ( Wang and Hauenstein, 2020 ). In innate immune cells derived from different AS animal models, upregulated NLRP3 expression was observed ( Liaqat et al, 2020 ). The importantance of NLRP3 inflammasome and its effectors, as well as their mediated pyroptosis in the development of AS has been proved by different investigations.…”

“…( Hoseini et al, 2018 ). Activated NLRP3 inflammasome causes consequent inflammation by inducing caspase-1 and various inflammatory cytokines like IL-1β and IL-18, and subsequently induces pyroptosis ( Liaqat et al, 2020 ). Since NLRP3 inflammasome involves the cross-talk between inflammation and lipid metabolism, intensively investigating its roles in AS and pharmacological interventions appears to be important for the prevention and treatment of AS.…”

Inflammation and Cardiovascular Disease: The Future

“…[ 52 ] The seminal role of the NLRP3 inflammasome and the IL-1β pathway in atherosclerosis have recently been reviewed in detail. [ 17 , 53 , 54 ]…”